Composite therapeutic film



Aug; 7, 1945.

F. c. SCHMELKES EIAL COMPOSITE THERAPEUTIC FILM FiIed Aug. 22, 1942 INVEN TORS Want? 6: St/mal/fesayfimrnk 1a delmw FITTORNEY Patented Aug. 7,1945 COMPOSITE THERAPEUTIC FILM Franz C. Schmelkes, Montclair, N. 1.,and Frederik J. G. de Leeuw, East Aurora, N. E, as-

H signers to Wallace & Tiernan Products Inc.. a

corporation of New Jersey Application August 22, 1942 Serial No. 5,975

1 Claim.

This invention relates to a therapeutic article in the form of a filmand particularly to such an article adapted for applying to a moistlesion two or more medicinals which, while chemically incompatible,react with each other only relatively slowly.

' Application of two or more therapeutic agents at the same time or insequence isoften desirable. Such instances are the use of twogermicides, a germicide and a local anaesthetic, or an anti-bacterialsubstance and a tissue growth stimulant. Preparations such as solutions,jellies, and ointments containing two or more therapeutic agents arefrequently impractical, particularly when chemical reaction between thevarious constituents reduces the shelf life oi such multiplepreparations.

The present invention provides a stable medicating article containingtwo or more therapeutic agents that may be chemically incompatible andpermits their simultaneous application in an effective, convenient andsimple manner. I

The invention comprises a therapeutic article including a hydrophilicbase material and a plurality of water soluble medicinal substancesdistributed in the base material. The major proportions and preferably,practically all of the said substances are isolated from each other bythe base material extending between the said substances, thisarrangement being particularly advantageous in those cases where themedicinal substances are slowly interreactive and injurious to eachother on relatively long contact. In the preferred embodiment, theinvention comprises loss of activity but that are not so quicklyreactive as to destroy each other to anobjectionable I extent in therelatively short period of time dur ing which the incompatiblesubstances are ditiusing from the composite and into-the body tissuewhen the composite is in use in a moist or weeping lesion.

The invention will be illustrated by descrip-- tion in connection withthe drawing to which reference is made. v

Figs. 1, 2, 3 and 4 show sectional views of the article of the presentinvention, the thickness being somewhat exaggerated in comparison withthe other dimensions.

a plurality of pliable substantially dry films and incompatiblemedicinals disposed separately in the several films so that no one filmwill contain substances that are incompatible with each other. Inanother embodiment, the invention comprises such a therapeutic filmcontaining a spacing layer, as of fabric or a thin non-medicated plasticor cementing layer that is readily penetrated by water, extendingbetween adjacent ones of the plurality of plies and maintaining theplies out of contact with each other. Preferably the one of the pliesthat is to be next to the lesion when the composite is in use isrelatively very thin, so as to offer a minimum of resistance todiffusion between the other ply and the lesion.

With a composite of the kind described, excellent results have beenobtained in the application of two or more medicating materials that,when maintained in long contact with each other as in solution in thesame film, undergo There are shown in Fig. 1 a plurality of films 2 and4 and in Fig. 2 like films with a cementing material 6 adhering thefilms together. In the structure of Fig. 3,,a spacing fabric 0 extendsbetween'two adjacent plies and is united to each of the plies which itserves to space from each other. In the structure of Fig. 4 there isshown a relatively thin film w joined to a much thicker film l2, thethinner film being the one that is in direct contact with the lesionwhen the article is in use. Because this film i0 is relatively verythin, it makes possible diiiusion at a satisfactory rate of medicantfrom film l2 to the lesion. The cement 6 serves also as a spacing layer.

In the figures, the thicknesses are somewhat exaggerated in relation toother dimensions. The various film members that have been described aswell as the cementing layer 6 must, be hydrophilic and, therefore,adapted to promote the diifusion of water and aqueous solutions of themedicants through the article. These films may be constituted largely orentirely of plastics that are hydrophilic and slowly soitenable by andultimately soluble in water'as, for example, methyl. cellulose (of whicha suitable grade is Methocel), polymerized vinyl alcoholoi plasticconsistency, and a cellulose derivative such as an ether of celluloseand glycolic acid or a slowly soluble salt of it. The term hydrophilic"as applied to the films or base materials is used to mean that the filmspermit the ready diffusion of aqueous liquid therein.

In addition to the base materials of hydrophilic nature, the filmsinclude also the selected medicating material. chemically incompatibleones being separated from each other by the film forming materialextending between the major proportions at least of such incompatiblesubstances. Suitably the incompatible substances are disposed separatelyin the several films. Thus, a germicide containing available chlorine iscontained in one of the individual films shown in the drawing and agermicide or local the relationship of any two of the films to eachotherbeing as illustrated in the drawing.

The cementing material used may be simply portions of the film formingmaterials adhered to each other, say surface portions that have beeninitially softened by vaporized solvent and then pressed together. Orthe cementing material may be some other hydrophilic, readily water'penetrable cement such as a very thinfilm of any one of the filmforming materials applied initially in a. suitable volatile solvent forsuch material, solvents for the film forming base materials disclosedbeing water, alcohol. acetone,

, or methanol, the organic solvents used contain ing some water.- Asolution of '15 parts of water. I and 25 parts of alcohol is aparticularly convenlent solvent for the cellulose ether. 1% use the wordsolvent to include any volatile liquid which may serve as a true solventor as a medium for a dispersion. Wherever we use the word soluassaeatamples of which are sulfanilamide itself, sulfathiasole, andsulfapyridine. The asochloramide' destroys anti -sulfanilamide bodiesknown to be present in infected wounds. Before use. the alcchloramideand the sulfanilamide compounds, known to be mutually destructive, arekept isolated in separate films .of the composite article. Preferablythe asochloramide is contained in the one of the films that is applieddirectly over the lesion when the article is in use. Theasochloramidesodisposedreachestbetistue ofthe lesion first and preparesthe site for the sulfa I drug. In this way the full activity of thesulfanilamide compound is preserved. It will be noted that the chemicalsare extracted in their original form, that is, without losing theirchemical identitles.

In general, the films are used in substantially drycondition. that is,of moisture content approximating that in equilibrium with the air orbelow that which causes development of objec- 'tlonable tackiness of thefilms. Also, the base tion, we include true solutions, colloidalsolutions, and dispersions.

The films are cast in a manner suitable for the casting of films ofplastic materials. Thus there is made a dope containing the desired filmforming material, the selected medicating substance or compatiblesubstances, and-a solvent for the base material and preferably also forthe medicating material present. Thus, there may be used a solvent ofthe kind mentioned above in connection with the formation of the cement.The dope so formed and of concentration to give to it a freely flowingto syrupy consistency is cast upon plate glassor other smooth surface,the solvent evaporated, and the remaining film stripped from the castingsurface and dried. The film is then plied with another film similarlymade," for instance, containing a dififerent medicinal that isincompatible with that in the first film. Films made as, described arenon-porous but water penetrable. c

When the spacing cloth is used, the preformed films may be pressedagainst the cloth sufficiently 0 contains medicant, is spread upon oneside of the cloth and a like solution of the incompatible medicant iscoated upon the other side in manner that is usual in the coating ofbothsides of fabrics with such compositions as pyroxylin solutions.

When the films are preformed before assembly.

- they may be made of predetermined desiredthickness. When they areformed by spreading upon the fabric member and then evaporating thevolatile solvent present, the film first formed is suitably maderelatively thick. After such impregnation then the second film isapplied as a rela-,

tively thin layer over one side of. the impregnated cloth, this thinnerfilm being applied directly over s moist lesion when the ,article is inuse.

The structure of the present invention is particularly useful inapplying medication with azomaterial of the films is preferablynon-metabolizable by microorganisms.

The invention will be further illustrated by detailed description inconnection with specific examples of the practice of the invention.

,. Example 1 A homogeneous paste is prepared from the followingmaterials: 27 parts Methocel, of viscosity 100 centipoises (cps.), 5.6parts glycerin, 3.75 parts sulfanilamide, 250 parts water and 250 partsethyl alcohol. This paste is applied to gauze using standard fabriccoating equipment and the solvents removed by evaporation. The paste isapplied in amounts sufficient to result in a weight of film of 1.5 to2.0 ounces per square yard exclusive of the weight of the fabric.

A second homogeneous paste is prepared from 40 parts of Methocel, 100cps., 10 parts triacetin, 1 part Azochloramide'(N,N'-dichloroazodicarbonamidine) and 500 parts of water. The abovecoated fabric is treated in a similar manner with the second paste at arate sufiicient to result in the film weighing 0.2 to 0.3 ounce persquare yard exclusive of the weight of fabric and sulfanilamidecontaining coating. The finished material is cut into the desired widthsand used as a therapeutic film.

f Example 2 Sixty parts of polyvinyl alcohol (type B, medium viscosity),12 parts glycerin, 8 parts sulfanilamide, 300 parts water and 400 partsethyl alcoholare mixedto a homogeneous solution. This solution is pouredinto drying trays in thin layers and the solvent caused to'evaporate bythe application of heat or exposure to dried air. To this dried filmthere is'added' a thin layer of a solution made from 30'parts Methocel,4000 cps., 1 part Azochloramide, 10 parts triacetin, 300 parts water and270 parts acetone. The solvents are removed by evaporation as before andthe double layered film is stripped from the drying tray and cut .into

the desired size. Bufilcient liquid is poured into the trays to'give thesulfanilamide containing layer a weight of 2 ounces per square yard andthe Azochloramide layer a weight of 0.2 to 0.3

ounce per square yard. This therapeutic film is normally used with theAzochloramide containing layer adjacent to the wound surface.

Example 3 A homogeneous paste made from 30 parts of polyvinyl alcohol(type 3 medium viscosity), 6 parts glycerin, 4 parts sulfadiazine, 150parts ethyl alcohol, and 200 parts water is applied to Cellophane in amanner described in Example 1, at such a rate. that the dried film willhave a weight of 1.5 to 1.8 ounce per square yard, exclusive of theweight of the Cellophane backer.

A second layer weighing 0.2 to 0.3 ounce per square yard after drying,is applied directly over the first layer. The paste used in the secondlayer is made from 25 parts of Methocel, 8 parts Azochloramide, 12 partstriacetin, 200 parts ethyl acetate and 250 parts acetone.

Example 4 parts of Methocel, 100 cps., 6 parts glycerine, 6 partssulfathiazole, 200 parts methyl alcohol and 300 arts water are worked upinto a homogeneous paste. This is applied to surgical gauze in a man-'ner described in Example 1, at the rate of 2.0 ounces per square yard.

A thin coating amounting to approximately 0.1 ounce per square yard isapplied over this first coating. This second layer consists oi!unplasticized Methocel and is obtained by coating the previous materialwith a thin solution 01 Methocel in methyl alcohol. It provides aneutral separating layer.

A third layer is applied at such a rate so as to result in a layerweighing 0.2 to 0.4 ounce per square yard. The material used inpreparingthis third layer consists of a homogeneous thin v paste composed of 50parts Methocel 15 cps., 5

parts triacetin, 1 part succinchloramide, and 300 parts water.

Example 5 Films weighing 1.5 to 2.5 ounces to the square yard may bemade, as described in any of the above numbered examples from acomposition including an alkaline buffer in conjunction with agermicidal sulfanilamide compound, the buffer establishing the pH whenthe film is in use at a pH of about 8 to 10, at which pH thesulfanilamide The compositions applied are in solution in a mixture ofalcohol and water, the non-volatile materials being as follows:

(1) '75 parts Methocel, 15 cps., 10 parts sulfanilamide, l0parts'glycerin, 1 part calcium carbonate, and 0.2 part sodium carbonate.

(2) 75 parts Methocel, 100 cps., 8 parts su1fa-' thiazole, 10 partsglycerine, and 1.5 parts secondary sodium phosphate.

(3) 75 parts polyvinyl alcohol, 5 parts sulfadiazine, 15 parts glycerin,0.2 part sodium carbonate, 1.0 part sodium bicarbonate and 1.0 partcalcium carbonate.

(4) 60 parts Methocel, 4,000 cps., 10 parts sulfanilamide, 10 partstriacetin, 1 part calcium carbonate, 0.8 part borax, and 0.2 part boricacid.

It will 'be understood that films made as described are preferablysterilized before use, as, for example, by autoclaving with steam for ashort period of time.

Certain subject matter herein disclosed but not claimed is covered inour copending application Ser. No. 456,458, flled on August 26, 1942,and enmum Sulfanilamide film.

It will be understood also that it is intended to coverall changes andmodifications oi the ex-- A dressing for a liquid exuding lesion whichcomprises a plurality of plies, at least one of which is thin, ofpliable, hydrophilic', non-porous but water penetrable material in fllmform, azochloramide distributed throughout the one of the said pliesthat is thin and that is to be in contact with the lesion when thedressing is in use, and a bacteriostatic sulianilamide compounddistributed throughout another of said plies, so that the azochloramideis extracted and reaches the lesion first after application of thedressing to the lesion and prepares the site for the sulfanilamidecompound in advance of contact of the sulfanilamide compound with thelesion.

FRANZ c. s. FREDERIKZ .1. n: narrow.

